Activation of Imprinted Gene Promotes Cardiac Fibrosis After Ischemic Injury.

Background: Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition in the myocardium, is an important target for heart disease treatments. (paternally expressed gene 3) is an imprinted gene expressed from the paternal allele, and de novo purine biosynthesis (DNPB) is a crucial pathway for nucleotide synthesis. However, the roles of PW1 and DNPB in ECM production by cardiac fibroblasts during myocardial ischemia are not yet understood.

Regulation of de novo and maintenance DNA methylation by DNA methyltransferases in postimplantation embryos.

DNA methylation is mainly catalyzed by three DNA methyltransferase (DNMT) proteins in mammals. Usually DNMT1 is considered the primary DNMT for maintenance DNA methylation, whereas DNMT3A and DNMT3B function in de novo DNA methylation. Interestingly, we found DNMT3A and DNMT3B exerted maintenance and de novo DNA methylation in postimplantation mouse embryos.

Epigenetic regulation in adult neural stem cells.

Neural stem cells (NSCs) exhibit self-renewing and multipotential properties. Adult NSCs are located in two neurogenic regions of adult brain: the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Maintenance and differentiation of adult NSCs are regulated by both intrinsic and extrinsic signals that may be integrated through expression of some key factors in the adult NSCs.

Efficient isolation of mouse deletion mutant embryonic stem cells by CRISPR.

Gene functions can be assessed in mouse embryonic stem (ES) cells and in mutant mice derived from mutant ES cells. Here, we describe an approach for efficient isolation of the ES clones carrying deletion mutations at the target genes by CRISPR-Cas9. Two sgRNAs against a target gene are co-expressed with puromycin-resistant gene in ES cells through co-transfection followed by transient puromycin selection.

Exerts Maternal and Sexually Dimorphic Effects on Genomic Imprinting.

has both maternal and zygotic functions in mouse. It maintains genomic imprinting at most known imprinted regions and controls allelic expression of the target imprinted genes in mouse embryos. The DNA methylation imprint at many imprinting control regions (ICRs) is lost when both maternal and zygotic are absent in maternal-zygotic mutant mouse embryos.

promoter methylation and its expression in valvular heart disease complicated with pulmonary artery hypertension.

Valvular heart disease (VHD) is a common heart disease that affects blood flow. It usually requires heart surgery. Valvular heart disease complicated with pulmonary artery hypertension (VHD-PAH) may be lethal due to heart failure that results from increased heart burden.

ZFP57 dictates allelic expression switch of target imprinted genes.

ZFP57 is a master regulator of genomic imprinting. It has both maternal and zygotic functions that are partially redundant in maintaining DNA methylation at some imprinting control regions (ICRs). In this study, we found that DNA methylation was lost at most known ICRs in mutant embryos.

Sex-dependent immune response and lethality of COVID-19.

COVID-19 has spread to all countries around the world after it was first discovered in Wuhan of China at the end of 2019. It is caused by a novel coronavirus called SARS-CoV-2 with much semblance to SARS-CoV including the sequence homology and disease symptoms. It is reported to be more infectious than SARS-CoV due to higher binding affinities between its spike protein and the ACE2 receptor on cell surface.

Effects of reprogramming on genomic imprinting and the application of pluripotent stem cells.

Pluripotent stem cells are considered to be the ideal candidates for cell-based therapies in humans. In this regard, both nuclear transfer embryonic stem (ntES) cells and induced pluripotent stem (iPS) cells are particularly advantageous because patient-specific autologous ntES and iPS cells can avoid immunorejection and other side effects that may be present in the allogenic pluripotent stem cells derived from unrelated sources. However, they have been found to contain deleterious genetic and epigenetic changes that may hinder their therapeutic applications.

Developing ABEmax-NG with Precise Targeting and Expanded Editing Scope to Model Pathogenic Splice Site Mutations In Vivo.

RNA splicing is related to many human diseases; however, lack of efficient genetic approaches to modulate splicing has prevented us from dissecting their functions in human diseases. Recently developed base editors (BEs) offer a new strategy to modulate RNA splicing by converting conservative splice sites, but it is limited by the editing precision and scope. To overcome the limitations of currently available BE-based tools, we combined SpCas9-NG with ABEmax to generate a new BE, ABEmax-NG.

Base-Editing-Mediated R17H Substitution in Histone H3 Reveals Methylation-Dependent Regulation of Yap Signaling and Early Mouse Embryo Development.

The coactivator-associated arginine methyltransferase CARM1 catalyzes the methylation of histone H3 arginine 17/26 (H3R17/26me) and non-histone proteins at arginine residues to regulate gene transactivation through profiling or Carm1 overexpression assays. However, the direct relationship between H3R17/26me and its causal role in mouse embryo development remains largely unclear. Here, we use rAPOBEC1-XTEN-Cas9n-UGI (BE3) to efficiently introduce a point mutation (R17H) at multiple Hist1/2H3 loci and a premature-stop codon into the catalytic domain of CARM1 in mouse embryos, resulting in remarkable downregulation of H3R17me levels and developmental defects in pre-implantation and fetal embryos.

Pericentral hepatocytes produce insulin-like growth factor-2 to promote liver regeneration during selected injuries in mice.

Unlabelled: Liver regeneration (LR) happens after various types of injuries. Unlike the well-studied LR caused by partial hepatectomy (PHx), there is accumulating evidence suggesting that LR during other injuries may result from unknown mechanisms. In this study, we found that insulin-like growth factor 2 (IGF-2) was drastically induced following the liver injuries caused by tyrosinemia or long-term treatments of CCl .

Zfp57 mutant ES cell lines directly derived from blastocysts.

Zfp57 is a master regulator of genomic imprinting in mouse embryos. To further test its functions, we have derived multiple Zfp57 mutant ES clones directly from mouse blastocysts. Indeed, we found DNA methylation imprint was lost at most examined imprinting control regions in these Zfp57 mutant ES clones, similar to what was observed in Zfp57 mutant embryos in the previous studies.

Derivation of hybrid ES cell lines from two different strains of mice.

Parental origin-dependent expression of the imprinted genes is essential for mammalian development. Zfp57 maintains genomic imprinting in mouse embryos and ES cells. To examine the allelic expression patterns of the imprinted genes in ES cells, we obtained multiple hybrid ES clones that were directly derived from the blastocysts generated from the cross between mice on two different genetic backgrounds.

lncRNA UCA1 inhibits esophageal squamous-cell carcinoma growth by regulating the Wnt signaling pathway.

Esophageal squamous-cell carcinoma (ESCC) is one of the most common tumors worldwide. Recent studies suggested that long noncoding RNAs (lncRNAs) might play a key role in regulating cellular processes and cancer progression. One of the lncRNAs, urothelial carcinoma associated 1 (UCA1), is known to be dysregulated in several cancers, including bladder carcinoma, colorectal, melanoma, breast, gastric, and ESCC.

Genomic imprinting defect in Zfp57 mutant iPS cell lines.

ZFP57 maintains genomic imprinting in mouse embryos and ES cells. To test its roles during iPS reprogramming,we derived iPS clones by utilizing retroviral infection to express reprogramming factors in mouse MEF cells. After analyzing four imprinted regions, we found that parentally derived DNA methylation imprint was largely maintained in the iPS clones with Zfp57 but missing in those without maternal or zygotic Zfp57.

Epigenetic Repression of miR-218 Promotes Esophageal Carcinogenesis by Targeting ROBO1.

miR-218, consisting of miR-218-1 at 4p15.31 and miR-218-2 at 5q35.1, was significantly decreased in esophageal squamous cell carcinoma (ESCC) in our previous study.

Differential regulation of genomic imprinting by TET proteins in embryonic stem cells.

TET proteins have been found to play an important role in active demethylation at CpG sites in mammals. There are some reports implicating their functions in removal of DNA methylation imprint at the imprinted regions in the germline. However, it is not well established whether TET proteins can also be involved in demethylation of DNA methylation imprint in embryonic stem (ES) cells.

Maternal and zygotic Zfp57 modulate NOTCH signaling in cardiac development.

Zfp57 is a maternal-zygotic effect gene that maintains genomic imprinting. Here we report that Zfp57 mutants exhibited a variety of cardiac defects including atrial septal defect (ASD), ventricular septal defect (VSD), thin myocardium, and reduced trabeculation. Zfp57 maternal-zygotic mutant embryos displayed more severe phenotypes with higher penetrance than the zygotic ones.

miRNA-183 suppresses apoptosis and promotes proliferation in esophageal cancer by targeting PDCD4.

In our previous study, miRNA-183, a miRNA in the miR-96-182-183 cluster, was significantly over-expressed in esophageal squamous cell carcinoma (ESCC). In the present study, we explored the oncogenic roles of miR-183 in ESCC by gain and loss of function analysis in an esophageal cancer cell line (EC9706). Genome-wide mRNA microarray was applied to determine the genes that were regulated directly or indirectly by miR-183.

Human and mouse ZFP57 proteins are functionally interchangeable in maintaining genomic imprinting at multiple imprinted regions in mouse ES cells.

Genomic imprinting is a common epigenetic phenomenon in mammals. Dysregulation of genomic imprinting has been implicated in a variety of human diseases. ZFP57 is a master regulator in genomic imprinting.

Genomic imprinting is variably lost during reprogramming of mouse iPS cells.

Derivation of induced pluripotent stem (iPS) cells is mainly an epigenetic reprogramming process. It is still quite controversial how genomic imprinting is reprogrammed in iPS cells. Thus, we derived multiple iPS clones from genetically identical mouse somatic cells.